This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human rhinovirus (HRV) and coxsackievirus (CV) are two members of the Picornaviridae family: HRV, a causative agent of the common cold, is a well studied pharmaceutical target with considerable structural information known about its complexes with antiviral compounds and receptor. Small molecule compounds bind to the HRV viral protein 1 (VP1) in an internal pocket located near the 5-fold symmetry axis of the capsid shell, and interrupt the virus life cycle by inhibiting the uncoating process. We propose the molecular mechanism for this antiviral activity involves long-range effects of antiviral compounds on conformational dynamics. Receptor recognition is another primary component of the virus life cycle. HRV and CV seem to recognize receptor largely by charge complementarity, but results from mutagenesis of a Lys residue cannot be explained from the known crystal structures. Conformational fluctuations of residues at the 5-fold axis are decreased when antiviral compounds occupy the VP1 pocket even though the pocket is not in direct contact with these residues. These long-range effects may be the origin of the antiviral activity of these compounds. The effects will be explored by MD simulations of the pentameric unit of HRV and complexes of HRV with WIN antiviral compounds. Similar studies on coxsackievirus A21 (CVA21) are also planned.